1. Technical Field
This invention relates generally to in-vitro diagnostics, and more particularly to disposable diagnostic cartridges and apparatus and methods for storing and delivering fluid to a diagnostic cartridge.
2. Related Art
Diagnostic tests are increasingly being used to determine the state or condition of a biological environment, such as in human healthcare, agriculture, live stock management, municipal systems management, and national defense, by way of example and without limitation. A new market is emerging wherein diagnostic tests are being performed at the point-of-care. The diagnostic test can be complex, requiring multiple fluids and multiple steps to execute an assay. An assay is a sequence of steps or procedures used measure the presence or absence of a substance in a sample, the amount of a substance in a sample, or the characteristics of a sample. An example of a common and relative simple point-of-care assay, which can be readily conducted by a layperson, is a blood glucose test. In this test, generally speaking, the blood is mixed with glucose oxidase, which reacts with the glucose in the sample, creating gluconic acid, wherein the gluconic acid reacts with a chemical, typically ferricyanide, producing ferrocyanide. Current is passed through the ferrocyanide and the impedance reflects the amount of glucose present.
Although the aforementioned blood glucose assay is relative common and simple, many assays are far more complex, in that they require specific fluids, often of differing types and quantities, to be stored for future use on the diagnostic device. These fluids may be, but are not limited to, a buffer solution for dilution, fluids containing antibodies and antigens, microspheres coated with binding agents, cell lysing agents, and other fluids required to manipulate the sample being tested. Diagnostic tests that utilize millifluidic and microfluidic volumes of the fluids are intended to provide an incredibly high degree of specificity, sensitivity, and a precise volume and rate of fluid delivery to achieve as accurate a test result as possible. Nearly all microfluidic tests require the introduction of fluids throughout the assay sequence to manipulate the sample being tested and to produce an accurate diagnosis.
Typically, consumable diagnostic devices, meaning the diagnostic device is disposable upon being used, require a companion durable hardware device that interfaces with the consumable diagnostic device to execute the test. The durable hardware performs many functions, one of which is to facilitate dispensing the fluids contained in a reservoir or reservoirs on the consumable diagnostic device into microfluidic or millifluidic channels formed within the consumable diagnostic device. Upon being urged to flow out of the reservoirs, the fluids can flow into a specimen containing reaction chamber. The introduction of the fluids to the reaction chamber requires precision; including flow rate, volume and timing, so as to best replicate the protocols of a laboratory where precession pipettes are employed.
Consumable diagnostic devices commonly include multiple fluid containing reservoirs, sometimes referred to as pouches, and more commonly referred to as blisters, sealed from environmental elements with the fluid being contained within the blister until the time of use. Several techniques have been devised to open the blisters to enable the fluid contained therein to be channeled to a reaction chamber. These techniques usually employ a mechanism that collapses, or crushes the blister under force, and a mechanism that forms an opening exiting the blister, thereby allowing the fluid to be pumped under force out of the blister, through the opening, and throughout the fluidic channels of the diagnostic device to the desired reaction chamber or chambers. The mechanism crushing the blister is typically performed slowly and continuously; however, the mechanism that forms the opening typically results in an uncontrolled “in-rush” of the fluid from the blister to the fluidic channels, which can be disruptive or destructive to the process, thereby having a negative impact on the ability to obtain accurate, reliable test results. This problem is compounded when multiple blisters are being crushed and opened in sequence or in parallel with one another, which is commonly done to promote mixing the fluids from the different blisters with one another, given multiple blister ruptures results in the uncontrolled in-rush of the various fluids from their respective ruptured blisters. Further yet, aside from the undesirable “in-rush” phenomenon, blisters can malfunction as a result of unwanted “delamination” of the blister.
The problem of “in-rush” results from the known construction the blisters. Currently, as shown in FIG. 1, with only a single blister assembly 1 being illustrated for simplicity, known blister assemblies are formed from a lamination of upper and lower film or flexible foil layers 2, 3 with one another, such as via a hot melt adhesive sandwiched therebetween, to form a bulbous portion, commonly referred to as blister 4, and a narrowed channel portion 5 extending from the bulbous portion 4 in the upper layer 2. The narrowed channel portion 5 has an upstream portion 6 in exposed, open fluid communication with the bulbous portion 4 and a downstream portion 7. The upstream and downstream portions 6, 7 are sealed off from one another by an intervening dam D formed by a portion of the upper and lower layers 2, 3 being locally bonded with one another, wherein the dam D is formed via the same adhesive, such as the aforementioned hot melt adhesive layer, and in the same process used to bond the periphery of the layers 2, 3 to one another. As such, the force required to delaminate and open the dam D is the same as the force required to delaminate the remaining portions of the upper layer 2 from the lower layer 3, including the outer periphery of the upper layer 2 from the lower layer 3.
The preformed blister assembly 1, with fluid contained within the bulbous portion 4, is bonded to an underlying substrate or base B of a diagnostic device 8 (FIGS. 1A, 1B), such that the downstream portion 7 of the channel portion 5 is positioned over a fluidic channel FC in the base B, wherein the fluid channel FC is in fluid communication with a downstream reaction chamber RC. The process of opening the blister assembly 1 typically involves compressing the bulbous portion 4 of the blister assembly 1 under a sufficient force to rupture the dam D, thereby causing an intentional delamination of the dam D, and thus, bringing the upstream portion 6 of the narrowed channel portion 5 into open fluid communication with the downstream portion 7, ultimately causing the fluid F from within the bulbous portion 4 to flow through the fluidic channel FC to the reaction chamber RC. However, this process presents multiple challenges, namely, the ability to control the flow rate of the fluid F from the bulbous portion 4 to the reaction chamber RC, and also, the ability to restrict the delamination of the upper layer 2 from the lower layer 3 to only the region of the dam D, while avoiding delamination elsewhere between the upper and lower layer 2, 3. Typically, the amount of force applied to the bulbous portion 4, often referred to as “actuation force”, in order to cause the dam D to delaminate is about 45 lbs or more, and as such, the relatively high actuation force required to rupture the dam D inherently causes a sudden burst of fluid flow past the dam D upon initial delamination thereof, thereby producing in the “in-rush” phenomenon. Further, the relatively high actuation force needed to delaminate the dam D inherently causes delamination between the upper and lower layers 2, 3 in areas other than the dam D, such as about the periphery of the bulbous portion 4, which in turn can result in an unintentional burst or leak from the periphery of the bulbous portion 4, thereby destroying the test. This occurs due to the fact that the dam D is formed by the same adhesive and bonding process that bonds of the upper and lower layers 2, 3 together.